Research Frontiers

Dr. Ron Kopito and Dr. Brigit Riley

Current research projects

Dr. Kopito mentions two current projects in his lab that he finds particularly exciting at the moment. The first project involves looking at the timing and appearance of inclusion bodies in HD. Dr. Kopito says he believes that to understand how IBs play a role in HD, he first has to know at what time point they appear over the course of the disease. When Ub accumulates and is incorporated into IBs, it indicates that something is wrong with the proteosome. Dr. Kopito thinks that this happens because at some point over the course of the disease, the proteosome just stops working. All of the extra Ub that should have been degraded needs somewhere to go, and it gets incorporated into an IB. But for Dr. Kopito, the question is when does that occur? When does the proteosome stop working? For more on the proteosome, UB, and HD click here and here.

To answer this question, the Kopito lab is using a model system with mice that have HD. They take samples from the brain tissues of these mice over time and test how well the proteosome is functioning at each time point in order to find the time when the proteosome stops working. Dr. Kopito says that the data from this experiment is forthcoming, and so they should have results to further investigate. He is pleased that he will be able to tell if his pet hypothesis (that the proteosome shuts down early and is important in the onset of HD) is right or wrong. Either way, it will give him a great direction in which to move his research.

Dr. Kopito’s second project is in partnership with a local biotechnology company. Together, they are trying to find biomarkers for HD. A biomarker for HD would be a type of molecule that indicates when neurodegeneration has started. A good marker could be a molecule that has a recognizable change in concentration or structure when neurodegeneration begins. It would be nice to have a biomarker for HD so that you do not have to wait for the motor, behavioral, or cognitive symptoms to appear to know when neurodegeneration has begun. (For more on the symptoms of HD, click here). Biomarkers would allow doctors and scientists to intervene in the course of the disease early on, before it is too late. Ideally, if you could test a blood sample and find a molecule that indicated that neurodegeneration had begun, it would be an important step in being able to test drugs and therapies.

This second project is actually closely related to the first project. Dr. Kopito hopes that the proteosome, or a piece of the proteosome, might be a good biomarker molecule for HD. If the experiments described for the first project prove that the proteosome stops functioning early in course of the disease, it could serve to indicate when it is time to intervene before the motor, behavioral, or cognitive symptoms set in. However, right now, the only ways to test how well the proteosome functions is by doing a biopsy, which is a complicated and very invasive procedure. Dr. Kopito proposes that a cerebral spinal tap might be an alternative, simpler option to test how well the proteosome is functioning.

Last Modified: 09/11/2007

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